Potassium channel blockers

Abstract

The present invention provides a compound of formula (I) or its salts or pharmaceutically acceptable derivatives wherein R 1 , R 2 , R 3 , X 1 , and A are defined herein. The compounds are useful as potassium ion channel inhibitors.

1. A compound of formula (I): 
       
         
           
           
               
               
           
         
         or its salts or pharmaceutically acceptable derivatives thereof, 
         wherein: 
         R 1  is selected from the group consisting of optionally substituted arylalkyl, wherein the substituents are selected from the group consisting of alkyl, cycloalkyl, —O—C(halogen) 3 , biaryl, carbocyclic aryl, heteroalicyclic, heteroaryl, acyl, amido, amino, alkyoxyamino, carbamoyl, carboxy, ether, hydroxy, imino, halo, nitro, sulfamoyl, sulfonyl, sulfinyl, sulfenyl, sulfonamido, and urea, optionally substituted aryl, wherein the substituents are selected from the group consisting of alkyl, cycloalkyl, —O—C(halogen) 3 , biaryl, carbocyclic aryl, heteroalicyclic, heteroaryl, acyl, amido, amino, alkyoxyamino, carbamoyl, carboxy, cyano, ether, hydroxy, imino, halo, nitro, sulfamoyl, sulfonyl, sulfinyl, sulfenyl, sulfonamido, and urea, optionally substituted heteroarylalkyl, wherein the substituents are selected from the group heteroalicyclic, heteroaryl, acyl, amido, amino, alkyoxyamino, carbamoyl, carboxy, cyano, ether, hydroxy, imino, halo, nitro, sulfamoyl, sulfonyl, sulfinyl, sulfenyl, sulfonamido, and urea, and optionally substituted heteroaryl, wherein the substituents are selected from the group consisting of alkyl, cycloalkyl, —O—C(halogen) 3 , biaryl, carbocyclic aryl, heteroalicyclic, heteroaryl, acyl, amido, amino, alkyoxyamino, carbamoyl, carbon, cyano, ether, hydroxy, imino, halo, nitro, sulfamoyl, sulfonyl, sulfinyl, sulfenyl sulfonamido, and urea; 
         R 2  is selected from the group consisting of optionally substituted acyl, optionally substituted sulfonyl and optionally substituted sulfamoyl; 
         R 3  is selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, aryloxy, optionally substituted alkyl, optionally substituted amino, optionally substituted amino carbonyl, optionally substituted amino or cyano; 
         X 1  is selected from a group consisting of a chemical bond, CR 7 R 8 , C(═O), C(═NH), NR 9 , NHC(═O), and SO 2 ; 
         wherein 
         R 7  and R 8  are independently selected from hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted aryl and optionally substituted heteroaryl or R 7  and R 8  together form an optionally substituted C 4-6  cycloalkyl ring; 
         R 9  is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted aryl and optionally substituted heteroaryl; 
         A represents an optionally substituted saturated or partially saturated 4-7 membered ring with the general formula: 
       
       
         
           
           
               
               
           
         
         or: 
       
       
         
           
           
               
               
           
         
         wherein: 
         X 2  is CH or N; 
         X 3  is CH 2 , CH(R 5a ), C(R 5a )(R 5b ), NH, N(R 5c ), O or S; 
         R 5a  and R 5b  for each occurrence is independently, halogen, optionally substituted amino, hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted alkanoyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; 
         R 5c  represents optionally substituted acyl, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; 
         X 4  is independently selected from the group consisting of C(═O), CH 2 , CH(R 4a ) and C(R 4a )(R 4b ); 
         R 4a  and R 4b  for each occurrence is independently halogen, optionally substituted amino, hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; and 
         n=1 or 2. 
       
     
     
       2. A compound according to  claim 1  where A is: 
       
         
           
           
               
               
           
         
         wherein: 
         X 3  is CH 2 , CH(R 5a ), C(R 5a )(R 5b ), NH, N(R 5c ) or O; 
         R 5a  and R 5b  independently represent halogen, optionally substituted amino, hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted alkanoyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; and 
         R 4a  and R 4b  independently represent halogen, hydroxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl. 
       
     
     
       3. A compound according to  claim 1  wherein:
 R 2  is selected from a group consisting of C(═O)R 10  and SO 2 R 10 ; 
 R 10  is selected from NR 11 R 12 , optionally substituted aryl, and optionally substituted heteroaryl; and 
 R 11  and R 12  are the same or different and each represents hydrogen, optionally substituted alkyl, optionally substituted aryl or optionally substituted heteroaryl. 
 
     
     
       4. A compound according to  claim 3  wherein R 10  is NR 11 R 12 . 
     
     
       5. A compound according to  claim 3  wherein R 10  is selected from a compound of formula (II), (III), (IV) or (V): 
       
         
           
           
               
               
           
         
         wherein: 
         G, J, L, D, and E are the same or different and each represents C or N with the provisos that in each instance: 
         1) at least one of G, J, L, D and E is N; 
         2) when R 10  is selected from compounds of formula (II), L may also represent O or S; and 
         3) when R 10  is selected from compounds of formula (III), G may also represent O or S; 
         R 13  and R 14  are the same or different and each represents hydrogen, halogen, hydroxy, optionally substituted C 1-3  alkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl or may be taken together to form an optionally substituted saturated or partially saturated 5-7 membered heterocyclic or carbocyclic ring; and 
         R 15 , R 16 , R 17 , R 18 , and R 19  are the same or different and each represents hydrogen, halogen, hydroxy, optionally substituted amino, cyano, optionally substituted C 1,3 -alkyl, and any of the pairs R 15  and R 16 , or R 16  and R 17 , or R 17  and R 18 , or R 18  and R 19  or may be taken together to form an optionally substituted saturated or partially saturated 5-7 membered heterocyclic or carbocyclic ring. 
       
     
     
       6. A compound according to  claim 1  where R 1  is selected from optionally substituted arylalkyl and optionally substituted heteroarylalkyl. 
     
     
       7. A compound according to  claim 1  wherein R 1  is a group of formula (VI): 
       
         
           
           
               
               
           
         
         wherein: 
         R 20 , R 21 , R 22 , R 23  and R 24  are the same or different and each represents hydrogen, halogen, hydroxy, optionally substituted amino, optionally substituted C 1-3  alkyl or optionally substituted alkoxy; 
         R 25  and R 26  are the same or different and each represents hydrogen, hydroxy, or optionally substituted C 1-3  alkyl. 
       
     
     
       8. A compound according to  claim 1  where R 3  is selected from hydrogen, halogen, hydroxy, cyano, and optionally substituted alkyl. 
     
     
       9. A compound according to  claim 8  wherein R 3  is selected from hydrogen, halogen and optionally substituted alkyl. 
     
     
       10. A compound according to  claim 1  wherein X 1  is selected from a chemical bond, CH 2 , and C(═O). 
     
     
       11. A compound according to  claim 1  of formula (VII): 
       
         
           
           
               
               
           
         
         wherein: 
         X 1  is selected from a group consisting of a chemical bond, CH 2 , and C(═O); 
         X 3  is CH 2 , CH(R 5a ), CH(R 5b ), NH, N(R 5c ) or O; 
         R 5a  and R 5b  independently represent halogen, optionally substituted amino, hydroxy, optionally substituted alkoxy, optionally substituted aryloxy, optionally substituted alkyl, optionally substituted alkanoyl, optionally substituted cycloalkyl, optionally substituted arylalky, optionally substituted aryl or optionally substituted heteroaryl; 
         R 5c  is optionally substituted C 1-3  alkyl, optionally substituted phenyl or optionally substituted heteroaryl; 
         X 4  is C(═O), CH 2 , CH(R 4a ) or C(R 4a )(R 4b ); 
         R 4a  and R 4b  independently represent halogen, hydroxy, optionally substituted aryloxy, optionally substituted C 1-3 alkyl, optionally substituted cycloalkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl; 
         R 3  is selected from the group consisting of hydrogen, halogen, and optionally substituted C 1-3  alkyl; 
         R 10  is NR 11 R 12  or a group of formula (II), (III), (IV) or (V): 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 11  and R 12  are the same or different and each represent optionally substituted G, J, L, D, and E are the same or different and each represents C or N with the provisos that in each instance: 
         1) at least one of G, J, L, D, or E is N; 
         2) when R 10  is formula (II), L may also represent O or S and 
         3) when R 10  is formula (III), G may also represent O or S; 
         R 13  and R 14  are the same or different and each represents hydrogen, halogen, hydroxy, optionally substituted C 1-3  alkyl, optionally substituted arylalkyl, optionally substituted aryl or optionally substituted heteroaryl or may be taken together to form an optionally substituted saturated or partially saturated 5-7 membered heterocyclic or carbocyclic ring; 
         R 15 , R 16 , R 17 , R 18 , and R 19  are the same or different and each represents hydrogen, halogen, hydroxy, optionally substituted amino, cyano, optionally substituted C 1-3  alkyl, and any of the pairs R 15  and R 16 , or R 16  and R 17 , or R 17  and R 18 , or R 18  and R 19  may be taken together to form an optionally substituted saturated or partially saturated 5-7 membered heterocyclic or carbocyclic ring; 
         R 20  R 21 , R 22 , R 23  and R 24  are the same or different and each represents hydrogen, halogen, hydroxy, optionally substituted amino, optionally substituted C 1-3  alkyl or optionally substituted alkoxy; and 
         n=1 or 2. 
       
     
     
       12. A compound as claimed in  claim 11  wherein R 5a  and R 5b  are independently fluoro, methyl, trifluoromethyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, optionally substituted phenyl, optionally substituted benzyl, optionally substituted phenethyl, hydroxy, substituted hydroxyethyl, hydroxypropyl, hydroxybutyl, optionally substituted phenoxy, optionally substituted benzyloxy, methoxyethyl, methoxypropyl, phenoxyethyl, benzyloxyethyl, acetyl, propionyl, substituted benzoyl, phenacyl, imidazoyl, pyrazoyl, pyridinoyl, oxadiazoloyl, thiazoloyl, acetamide, methylacetamide, dimethylacetamide, ethylacetamide, diethylacetamide, tert-butylacetamide, pyridylacetamide, cyclopropylacetamide, cyclobutylacetamide, cyclopentylacetamide, or cyclohexylacetamide. 
     
     
       13. A compound as claimed in  claim 12  wherein R 5a  and R 5b  are independently fluoro, optionally substituted methyl, hydroxy, optionally substituted cyclohexyl, optionally substituted phenyl, optionally substituted benzyl, optionally substituted phenoxy, optionally substituted benzyloxy, or thiazoloyl. 
     
     
       14. A compound according to  claim 11  wherein the group of formula (II), (III), (IV) or (V) is substituted imidazole, substituted pyrazole, substituted pyrrole, substituted oxazole, substituted oxadiazole, substituted thiazole, substituted thiadiazole, substituted pyridine, substituted pyrimidine, substituted pyrazine, substituted pyridazine, substituted triazine, substituted phenyl, tetrahydrobenzofuran, benzopyran, dihydrobenzodioxin, benzoxazinone, benzooxadiazole, benzodioxole, indoline, indole, indazole, or benzomorpholine. 
     
     
       15. A compound according to  claim 14  wherein the group of formula (II), (III), (IV) or (V) is substituted imidazole, substituted pyrazole, substituted pyridine, phenyl, fluorophenyl, cyanophenyl, tetrahydrobenzofuran, benzopyran, dihydrobenzodioxin, benzoxazinone, benzooxadiazole, benzodioxole, indoline, or benzomorpholine. 
     
     
       16. A compound selected from the group consisting of:
 N-(4-Chloro-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(2-Chloro-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(3-Chloro-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(4-Fluoro-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 Naphthalene-2-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-3,4-dimethoxy-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 2,3-Dihydro-benzo[1,4]dioxine-6-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-4-methyl-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 Thiophene-2-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 Thiophene-3-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-4-fluoro-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-2-fluoro-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-3-fluoro-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-4-cyano-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-3-cyano-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-2-cyano-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-2-methyl-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-3-methyl-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-3-methoxy-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-3,5-dichloro-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-3-chloro-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(3-Fluoro-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(2-Methoxy-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(3-Methoxy-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(2-Methyl-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(4-Methyl-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-[4-(4-Phenyl-piperazine-1-carbonyl)-phenyl]-N-(4-trifluoromethyl-benzyl)-benzenesulfonamide; 
 N-[4-(4-Phenyl-piperazine-1-carbonyl)-phenyl]-N-(3-trifluoromethoxy-benzyl)-benzenesulfonamide; 
 N-(2-Cyano-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(4-Cyano-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 2,2-Dimethyl-chroman-6-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-4-nitro-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 Furan-2-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-N-[3-methyl-4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[2-fluoro-4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[3-methoxy-4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[4-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-phenyl]-benzenesulfonamide 
 N-Benzyl-N-[4-(2,6-dimethyl-morpholine-4-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[4-(piperidine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-4-ethyl-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[4-(4-hydroxy-4-phenyl-piperidine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-Benzyl-N-[4-(4-benzyl-4-hydroxy-piperidine-1-carbonyl)-phenyl]-benzene sulfonamide; 
 N-(2,3-Dimethoxy-benzyl)-N-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(4-Chloro-benzyl)-N-[4-(3-p-tolyl-piperidine-1-carbonyl)-phenyl]-benzenesulfonamide; 
 N-(4-Chloro-benzyl)-N-{4-[3-(4-methoxy-phenyl)-piperidine-1-carbonyl]-phenyl}-benzenesulfonamide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[2-methyl-4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[2-fluoro-4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-methyl-benzyl)-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (3-fluoro-benzyl)-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (3-methoxy-benzyl)-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-chloro-benzyl)-{4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-piperidine-1-carbonyl]-phenyl}-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-chloro-benzyl)-[4-(3-phenyl-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid 4-chloro-benzyl)-[4-(3-phenoxy-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(2-phenyl-morpholine-4-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(3-phenyl-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-{4-[3-(3-methyl-[1,2,4]oxadiazol-5-yl)-piperidine-1-carbonyl]-phenyl}-amide; 
 1,3-Dimethyl-1H-pyrazole-4-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 2,3-Dimethyl-3H-imidazole-4-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 2,4-Dimethyl-thiazole-5-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4-phenyl-piperazine-1-ylmethyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[2-fluoro-4-(2-phenyl-morpholine-4-carbonyl)-phenyl]-amide; 
 N-Benzyl-N-[4-(2-phenyl-morpholine-4-carbonyl)-phenyl]-dimethylsulfamide; 
 N-Benzyl-N-[4-(2-phenyl-morpholine-4-carbonyl)-3-fluorophenyl]-dimethylsulfamide; 
 N-(4-Fluoro)benzyl-N-[4-(2-phenyl-morpholine-4-carbonyl)-phenyl]-dimethylsulfamide; 
 4-{4-[Benzyl-(1-methyl-1H-imidazole-4-sulfonyl)-amino]-benzoyl}-2-phenyl-piperazine-1-carboxylic acid tert-butyl ester; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-{4-[3-(4-fluoro-phenyl)-pyrrolidine-1-carbonyl]-phenyl}-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-chloro-benzyl)-[4-(piperidine-1-carbonyl)-phenyl]-amide; 
 N-Benzyl-N-{4-[4-(2-cyano-phenyl)-piperazine-1-carbonyl]-phenyl}-dimethylsulfamide; 
 N-Benzyl-N-{4-[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidine-1-carbonyl]-phenyl)-dimethylsulfamide; 
 N-Benzyl-N-[4-(3-benzyloxy-pyrrolidine-1-carbonyl)-phenyl]-dimethylsulfamide; 
 N-Benzyl-N-[4-(4-hydroxy-4-phenyl-piperidine-1-carbonyl)-phenyl]-dimethylsulfamide; 
 N-Benzyl-N-[4-(4-phenoxy-piperidine-1-carbonyl)-phenyl]-dimethylsulfamide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4-methyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(3-methyl-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-{4-[4-(2-fluoro-phenyl)-piperazine-1-carbonyl]-phenyl}-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4-cyclohexylmethyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4-methyl-3-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4-thiazol-2-yl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(3-trifluoromethyl-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(4,4-difluoro-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid benzyl-[4-(3-fluoro-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-pyrazole-3-sulfonic acid benzyl-[4-(2-phenyl-morpholine-4-carbonyl)-phenyl]-amide; 
 2-Methyl-2H-pyrazole-3-sulfonic acid benzyl-[4-(2-phenyl-morpholine-4-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-pyrazole-3-sulfonic acid (4-chloro-benzyl)-[4-(piperidine-1-carbonyl)-phenyl]-amide; 
 Pyridine-3-sulfonic acid (4-chloro-benzyl)-[4-(piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-pyrazole-3-sulfonic acid benzyl-[4-(3-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 2-Methyl-2H-pyrazole-3-sulfonic acid benzyl-[4-(3-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-pyrazole-3-sulfonic acid benzyl-[4-(4-methyl-3-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 2-Methyl-2H-pyrazole-3-sulfonic acid benzyl-[4-(4-methyl-3-phenyl-piperazine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-chloro-benzyl)-[4-(3-methyl-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (3-chloro-benzyl)-[4-(piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-fluoro-benzyl)-[4-(3-methyl-piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-methyl-benzyl)-[4-(3-methy piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (3,4-dichloro-benzyl)-[4-(piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (3-chloro-4-fluoro-benzyl)-[4-(piperidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-chloro-benzyl)-[4-(2-methyl-pyrrolidine-1-carbonyl)-phenyl]-amide; 
 1-Methyl-1H-imidazole-4-sulfonic acid (4-chloro-benzyl)-[4-(3-methyl-pyrrolidine-1-carbonyl)-phenyl]-amide; and 
 1-Methyl-1H-imidazole-4-sulfonic acid 4-chloro-benzyl)-[4-(3,3-difluoro-pyrrolidine-1-carbonyl)-phenyl]-amide; 
 and pharmaceutically acceptable salts thereof. 
 
     
     
       17. A pharmaceutical composition comprising at least one compound as claimed in  claim 1  and one or more pharmaceutically acceptable excipients, diluents and/or carriers. 
     
     
       18. A compound as claimed in  claim 11 , wherein:
 R 11 , R 12 , R 13  and R 14  are each CH 3 ; 
 R 4a  and R 4b  are independently fluoro, optionally substituted methyl, hydroxy, trifluoromethyl, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted benzyloxy or optionally substituted oxadiozole; and 
 R 20 , R 21 , R 22 , R 23  and R 24  are independently selected from hydrogen, fluoro, chloro and methyl.